Delineating the lipidated Atg8 structure for unveiling its hidden activity in autophagy
Delineating the lipidated Atg8 structure for unveiling its hidden activity in autophagy
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DOI：
10.1080/15548627.2021.1961075
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发表时间：
2021-08
期刊：
影响因子：
13.3
通讯作者：
Tatsuro Maruyama;N. Noda
中科院分区：
文献类型：
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作者：
Tatsuro Maruyama;N. Noda
摘要ATG8作为自噬小体生物发生的中心因子，长期以来一直受到人们的关注。然而，作为生理功能脂化形式的Atg8在吞噬体膜上的分子活性仍然是个谜。在我们最近的研究中，我们揭示了脂化的ATG8向膜的隐藏的物理化学活性。结构分析表明，脂化的Atg8在膜上采取了优先取向，使用芳香族残基接触膜，同时将货物结合袋暴露在溶剂中，使这种小蛋白能够在识别自噬货物的同时扰动和转化膜。膜扰动活性被证明是有效的自噬小体生物发生所必需的，然而关于Atg8的机制作用的问题仍然悬而未决。
ABSTRACT Atg8 has attracted attention as a central factor in autophagosome biogenesis for a long time. However, the molecular activities of Atg8 on the phagophore membranes as the physiologically functional lipidated form remain enigmatic. In our recent study, we unveiled the hidden physicochemical activity of lipidated Atg8 toward the membrane. Structural analysis revealed that lipidated Atg8 adopts a preferred orientation on the membrane, contacting the membrane using aromatic residues and at the same time exposing cargo binding pockets to the solvent, enabling this small protein to perturb and transform membranes while recognizing autophagic cargos. The membrane perturbation activity was shown to be essential for efficient autophagosome biogenesis, yet questions on the mechanistic roles of Atg8 remain open.